Protein Kinase CK2 Regulates CDC25B Phosphatase Activity

Oncogene. 2003 Jan 16;22(2):220-32. doi: 10.1038/sj.onc.1206107.

Abstract

Human dual-specificity phosphatases CDC25 (A, B and C) play an important role in the control of cell cycle progression by activating the cyclin-dependent kinases (CDKs). Regulation of these phosphatases during the cell cycle involves post-translational modifications such as phosphorylation and protein-protein interactions. Given the suspected involvement of the protein kinase CK2 at the G2/M transition, we have investigated its effects on the CDC25B phosphatase. We show that in vitro CK2 phosphorylates CDC25B, but not CDC25C. Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. We also report that CDC25B interacts with CK2, and this interaction, mediated by the CK2beta regulatory subunit, involves domains that are located within the first 55 amino acids of CK2beta and between amino acids 122 and 200 on CDC25B. This association was confirmed in vivo, in Sf9 insect cells and in U(2)OS human cells expressing an HA epitope-tagged CDC25B. Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo. We discuss the possibility that CDC25B phosphorylation by CK2 could play a role in the regulation of the activity of CDC25B as a starter of mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Casein Kinase II
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Epitopes / genetics
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Serine / metabolism
  • Spodoptera / cytology
  • Up-Regulation
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism*

Substances

  • Cell Cycle Proteins
  • Epitopes
  • Peptide Fragments
  • Recombinant Proteins
  • casein kinase 2 beta (1-16)
  • Serine
  • Protein Kinases
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • CDC25B protein, human
  • CDC25C protein, human
  • cdc25 Phosphatases